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Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60% increase of myocardial incorporation of lysine-14 C into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The fall-off in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in total coronary flow or pressure. A 60% increase in coronary perfusion was associated with a similar response of protein synthesis to progressive elevations of pressure. Since the ATP levels rose and lactate production fell, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 hr did not result in increased protein incorporation of lysine-14 C. The studies indicate a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se and suggest a pressure receptor triggering protein synthesis within the ventricular wall. Such a relationship is not apparent in short term volume loading in vitro.

The occurrence of cardiomy opathy in chronic alcoholics is well known, but the causes are as yet unclear (Mitchell and Cohen, 1970). Metabolic effects of ethanol, such as accumulation of triglycerides despite a decrease in fatty acid extraction (Regan et al., 1966; 1969), have been suggested as a cause of ultimate impairment of myofibrillar function. The suggestion has also been made that the detrimental effects of ethanol may actually be an acetaldehyde effect, mediated through the release of norepinephrine causing chronic chronotropic and inotropic effects which may often play a role in the development of the myopathy (James and Bear, 1967). It has been reported that acute exposure to alcohol decreases to one-third that of the control the capacity of the liver to synthesize albumin (Rothschild et al., 1971). In view of the rapid inhibitory effect, it was felt to be of interest to study the effect of alcohol in the perfused heart to see whether myocardial protein synthesis was similarly inhibited. In addition, since alcohol is apparently not metabolized by the heart (Gailis and Verdy, 1971; Lochner, Cowley, and Brink, 1969). The effect of a primary metabolite, acetaldehyde (James and Bear, 1967), synthesized in liver was also studied. The results indicated that acute exposure to levels of alcohol which decreased albumin synthesis in the perfused liver had no effect on protein synthesis in the perfused heart. However, acetaldehyde, at levels that produce a marked chronotropic and inotropic effect, markedly inhibited protein synthesis of total cardiac protein. To further define the inhibition of protein synthesis by acetaldehyde, the effects of ethanol and acetaldehyde on cardiac micorsomes were also studied in cell-free systems. Some of these data were reported previously (Schreiber et al., 1972; 1974).